Raphela-Choma Portia, Motadi Lesetja, Simelane Mthokosizi, Choene Mpho
Department of Biochemistry, University of Johannesburg, Corner Kingsway and University Road, Auckland Park, Johannesburg, 2092, South Africa.
Rep Biochem Mol Biol. 2024 Jan;12(4):586-595. doi: 10.61186/rbmb.12.4.586.
Pancreatic cancer and colon cancer pose significant challenges in treatment, with poor prognoses. Natural products have long been explored for their potential as anticancer agents. Iso-mukaadial acetate has shown promise in inducing apoptosis in breast and ovarian cancer cells. The objective of this study was to investigate the effect of Iso-mukaadial acetate on pancreatic (MIA-PACA2) and colon (HT29) cancer cell lines.
Pancreatic (MIA-PACA2) cancer cells, colon (HT29) cancer cells, normal embryonic kidney cells (HEK 293), and normal lung cells (MRC5) were cultured and treated with Iso-mukaadial acetate (IMA) for 24 hours. The viability assays were conducted using Alamarblue reagent and a real-time cell viability monitoring system, xCELLigence. The IC values were determined, followed by assessments of ATP production, caspase 3/7 activation, mitochondrial function, morphological changes using a light microscope, and gene expression changes via RT-PCR.
This study indicates that Iso-mukaadial acetate exhibited concentration-dependent cytotoxic effects, slowing cellular proliferation in both cancer cell lines. Activation of the mitochondrial apoptotic pathway and caspase 3/7 suggests induction of apoptosis. Reduced ATP production and altered gene expression further support its anticancer properties. Morphological changes after treatment with Iso-mukaadial acetate showed apoptotic characteristics which may suggest that apoptosis was induced.
According to the results obtained, Iso-mukaadial acetate shows potential as an anticancer agent, evidenced by its effects on cellular viability, mitochondrial function, ATP production, caspase activation, and gene expression in pancreatic and colon cancer cells. These findings highlight its promise for further investigation and potential in the development of therapeutic agents.
胰腺癌和结肠癌在治疗方面面临重大挑战,预后较差。长期以来,人们一直在探索天然产物作为抗癌剂的潜力。异穆卡地尔乙酸酯已显示出诱导乳腺癌和卵巢癌细胞凋亡的前景。本研究的目的是调查异穆卡地尔乙酸酯对胰腺(MIA-PACA2)和结肠(HT29)癌细胞系的影响。
培养胰腺(MIA-PACA2)癌细胞、结肠(HT29)癌细胞、正常胚胎肾细胞(HEK 293)和正常肺细胞(MRC5),并用异穆卡地尔乙酸酯(IMA)处理24小时。使用Alamarblue试剂和实时细胞活力监测系统xCELLigence进行活力测定。确定IC值,随后评估ATP生成、半胱天冬酶3/7激活、线粒体功能、使用光学显微镜观察形态变化以及通过RT-PCR检测基因表达变化。
本研究表明,异穆卡地尔乙酸酯表现出浓度依赖性细胞毒性作用,减缓了两种癌细胞系中的细胞增殖。线粒体凋亡途径和半胱天冬酶3/7的激活表明诱导了细胞凋亡。ATP生成减少和基因表达改变进一步支持了其抗癌特性。用异穆卡地尔乙酸酯处理后的形态变化显示出凋亡特征,这可能表明诱导了细胞凋亡。
根据获得的结果,异穆卡地尔乙酸酯显示出作为抗癌剂的潜力,其对胰腺和结肠癌细胞的细胞活力、线粒体功能、ATP生成、半胱天冬酶激活和基因表达的影响证明了这一点。这些发现突出了其进一步研究的前景以及在治疗剂开发中的潜力。